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Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 You, Wen, Tian, Lv, Li, Li, Xin, Li, Zhang and Zhang.)

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is involved in lipid metabolism of various tissues. Different metabolites of fatty acids and agonists like fibrates activate PPARα for its transactivative or repressive function. PPARα is known to affect diverse human diseases, and we focus on advanced studies of its transcriptional regulation in these diseases. In MAFLD, PPARα shows a protective function with its upregulation of lipid oxidation and mitochondrial biogenesis and transcriptional repression of inflammatory genes, which is similar in Alzheimer's disease and cardiovascular disease. Activation of PPARα also prevents the progress of diabetes complications; however, its role in diabetes and cancers remains uncertain. Some PPARα-specific agonists, such as Wy14643 and fenofibrate, have been applied in metabolic syndrome treatment, which might own potential in wider application. Future studies may further explore the functions and interventions of PPARα in cancer, diabetes, immunological diseases, and neurodegenerative disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Wang and Li.)

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase-activating protein (GAP) and modulate integrin-mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Introduction: A number of miRNAs have been reported to be critically involved in the regulation of cardiovascular disease (CVDs). Therefore, the development of potent analogues/inhibitors for miRNAs have thus become a key focus in the present drug discovery. In this review, we discuss the basic research and clinical use of miRNAs as the early diagnosis and therapeutic targets for CVD. We have also focused on the efficiency of therapeutically targeting miR-499, which is considered as one of the most promising molecules for treating CVDs. Areas covered: In this review, we have discussed the patents and patent applications related to miRNAs detected in CVD patients published in recent years. This review also covers the expression pattern of miR-499, as well as it highlights functions of its inhibitors in CVD. We used Google and Pubmed search engines to find relevant patents. Expert opinion: Although a massive number of miRNAs are patented as CVD biomarkers, further work is absolutely required to evaluate the reliable diagnostic values and therapeutic potential of these candidates. Overall, targeting miRNAs is definitely a promising strategy to be investigated for diagnosis and treatment of CVDs in future, however, the delivery system and off-targets effects are still a difficult challenge need to be elucidated.

Mitochondrial dynamics play a critical role in cellular responses and physiological process. However, their dysregulation leads to a functional degradation, which results in a diverse array of common disorders, including cardiovascular disease. In this background, the mitochondrial ubiquitin ligase has been attracting substantial research interest in recent years. Mitochondrial ubiquitin ligase is localized in the mitochondrial outer membrane, where it plays an essential role in the regulation of mitochondrial dynamics and apoptosis. In this chapter, we provide a comprehensive overview of the functions of mitochondrial ubiquitin ligases identified hitherto, with a special focus on cardiovascular disorders.

MicroRNAs (miRNAs) have been considered important regulators in both physiological and disease contexts. Among all miRNAs, the miR-34 family (miR-34a, -34b, -34c), which has been well characterized as a tumor suppressor, displays diverse functions in noncancerous diseases. MiR-34 levels are relatively low in the cardiovascular system, but recently they have been reported to function in cardiovascular disorders by regulating apoptosis, telomere attrition, DNA damage, and inflammatory response. In this review, we mainly summarize their roles in cardiac senescence and ischemic diseases.

Brain-derived neurotrophic factor (BDNF) is one of the most abundantneurotrophins in the central nervous system. Numerous studies suggestthat BDNF has extensive roles by binding to its specific receptor, tropomyosin-related kinase receptor B (TrkB), and thereby triggering downstream signaling pathways. Recently, growing evidence highlightsthat the BDNF/TrkB pathway is expressed in the cardiovascular system andclosely associated with the development and outcome of cardiovascular diseases (CVD), including coronary artery disease, heart failure, cardiomyopathy, hypertension, and metabolic diseases. Furthermore, circulating BDNF has also been revealed as a new potential biomarker for both diagnosis and prognosis of CVD. In this review, we discuss the current evidence of the emerging role of BDNF/TrkBsignalingand address the challenges that remain in translating these discoveries to novel therapeutic strategies for CVD. [ABSTRACT FROM AUTHOR]

Angiogenesis is the physiological process of new blood vessel formation from existing capillary vessels or posterior capillary veins. Its dysfunction could result in a number of diseases, such as cardiovascular diseases and cancer, contributing to death and disability worldwide. Circular RNAs (circRNAs) are a class of novel identified RNA molecules with a special covalent loop structure without a 5′ cap and 3' tail, which can lead to novel back-splicing or skipping events from precursor mRNAs. Accumulating evidence suggests that circRNA play critical roles in diseases; in particular, they are abundantly and abnormally expressed in angiogenesis-related diseases. In this review, we describe the role of circRNA under pathological conditions, discuss the association between circRNA and angiogenesis, classify the regulatory mechanisms and suggest that circRNA can be used as potential therapeutic targets for angiogenesis-related diseases under clinical evaluation. Image 1 • circRNAs are critically involved in angiogenesis, angiocardiopathy and cancer. • circRNAs are stable and abundantly distributed indicating a potential role in diseases. • circRNA might target miRNA as a sponge and are an emerging therapeutic target for angiogenesis-related diseases. • The research of coding potential of circRNA suggests the possible effective treatment of related diseases in the future. [ABSTRACT FROM AUTHOR]

Summary MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3′ UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases. Here we report that miRNAs can be oxidatively modified by ROS. We identified that miR-184 upon oxidative modification associates with the 3′ UTRs of Bcl-xL and Bcl-w that are not its native targets. The mismatch of oxidized miR-184 with Bcl-xL and Bcl-w is involved in the initiation of apoptosis in the study with rat heart cell line H9c2 and mouse models. Our results reveal a model of ROS in regulating cellular events by oxidatively modifying miRNA. [ABSTRACT FROM AUTHOR]